〔Abstract〕 Objective To analyze the factors of positive margin after LEEP knife cervical conization in patients with high-grade squamous intraepithelial lesion (HSIL). Methods 100 patients with HSIL were selected for a retrospective analysis from January 2018 to March 2021 in Huizhou First Maternal and Child Health Care Hospital, and the factors of positive cervical margin after LEEP knife conical resection were analyzed. Results Univariate analysis showed that the type of Human papillomavirus (HPV) infection, lesion grade and whether the lesion involved the gland were the influencing factors for the residual lesion after cervical conectomy (P < 0.05). Multivariate logistic regression analysis showed that multiple HPV infections and lesion grades were independent risk factors for residual lesions after cervical conectomy (P < 0.05). Conclusion Multiple HPV infections and lesions of HSIL patients with LEEP knife cervical coning are independent risk factors for residual lesions. Clinical care should be carried out for these patients and regular review should be urged to detect residual lesions early.